Advancing microstructural and vascular neuroimaging in perinatal stroke The overall objective of this research is to dramatically improve early diagnosis and prognosis of perinatal stroke to identify the best management options and therapeutic targets for patients with a poor prognosis. Magnetic resonance imaging (MRI) is considered a safe and sensitive tool for the diagnosis and evaluation of perinatal stroke and the response of the rapidly growing young brain to this injury. Advanced MRI techniques, in particular, diffusion-compartment imaging (DCI), susceptibility-weighted MRI (SWI), and magnetic resonance angiography (MRA) are considered crucial components of a clinical imaging protocol to evaluate stroke and brain injury. The application of these techniques in the fetal period, however, is extremely challenging because of the small signal available from the small fetal neural and vascular structures and the intermittent fetal and maternal motion that disrupts the spatial encoding necessary for these typically lengthy MRI scans. Postnatal MRI poses similar challenges, particularly with respect to small head movements, which produce significant artifacts in longer acquisitions. Sedation, which is used to immobilize infants and very young children, is invasive and potentially harmful; and thus, cannot be used in research studies. There is a critical need, therefore, for motion-robust, high-resolution, advanced MRI technologies to evaluate neural and neurovascular structures in the fetus and neonate. The lack of such imaging technology significantly limits clinical evaluation and prognosis, as well as research on perinatal stroke. This project aims to fill these gaps in technology through the development of innovative, motion-robust, high-resolution MRI sequences, specifically, DCI, SWI, and MRA to evaluate neurovascular microstructure, cerebral vascular malformations, and brain network injury after perinatal stroke. The three specific aims of this project are to 1) develop motion robust DCI to evaluate altered brain microstructure and connectivity in perinatal stroke; 2) develop motion-robust technology for SWI for the fetus and newborn; and 3) develop motion-robust MRA for the fetus and newborn. These contributions are important because they will 1) enable in-vivo high-resolution imaging of the neurovascular structure, brain network, and injury in the fetal and newborn brain; and 2) significantly improve the use of advanced MRI technologies to assess perinatal stroke and brain development following perinatal stroke, both in the clinic and in research settings. The technology developed and knowledge obtained from this study will lead to improved diagnosis and prognosis of perinatal stroke, and will significantly improve studies and trials that aim to reduce the burden of related neurological disorders such as cerebral palsy and epilepsy through timely therapeutic interventions, i.e., anticoagulant therapy, stem cell therapies, brain hypothermia, brain stimulation, and developmental and educational therapies.